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PubMed2005

Gestational exposure to hydroxyprogesterone caproate suppresses reproductive potential in male rats.

Hydroxyprogesterone caproate was administered to pregnant rats at a dose level of 10 and 25 mg/kg body weight on 1st, 7th and 14th gestational day and the male pups (F1 generation) were allowed to grow for 90 days. The effect of gestational exposure to hydroxyprogesterone caproate on fertility was assessed by breeding F1 male rats with control female rats besides analyzing sperm quality and quantity in F1 male rats. The number of implantation sites and viable fetuses was significantly reduced in females mated with F1 males that were exposed to hydroxyprogesterone caproate during embryonic development. The decrease in sperm function was associated with a decrease in sperm motility, sperm viability and sperm count in F1 rats. The study clearly indicates that in utero exposure to hydroxyprogesterone caproate affects fertility in male rats.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1984

Product inhibition of steroid-17 alpha-monooxygenase by endogenous 17 alpha-hydroxyprogesterone in microsomes and isolated Leydig cells from rat testis.

Use of integrated rate equations for analysis of progesterone metabolism by isolated Leydig cells and microsomes from rat testis in presence of several progesterone concentrations within several periods reveals competitive product inhibition by endogenously formed 17 alpha-hydroxyprogesterone (Kpm = 0.1 microM) of steroid-17 alpha-monooxygenase activity (Ksm = 0.8 microM). The discrepancy between this very low interaction constant of endogenous 17 alpha-hydroxyprogesterone with the steroid-17 alpha-monooxygenase, and the respective values (from the literature) for exogenous 17 alpha-hydroxyprogesterone which are about 50-fold higher, may be explained by accumulation of endogenous 17 alpha-hydroxyprogesterone at the catalytic site of the steroid-17 alpha-monooxygenase. This mechanism may be important for intratesticular regulation of androgen biosynthesis from precursor steroids.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Blood-spot 17-hydroxyprogesterone daily profiles in infants with congenital adrenal hyperplasia.

To define the optimum blood levels of 17-hydroxyprogesterone, the hormonal effects of glucocorticoid treatment were studied during the neonatal period and infancy in 20 patients with 21-hydroxylase deficiency. Repeated daily profiles of blood spot 17-hydroxyprogesterone were used to monitor therapy and these data were related to serum concentrations of testosterone. A wide fluctuation of blood 17-hydroxyprogesterone levels was observed in patients with a mean daily value higher than 150 nmol/l indicating poor control. Serum testosterone levels decreased into normal range in female patients with blood-spot 17-hydroxy-progesterone levels between 50 and 150 nmol/l. Daily profiles with mean values less than 50 nmol/l showed low magnitude of circadian variation suggesting overtreatment. We conclude that the daily profile of blood-spot 17-hydroxyprogesterone is a practical alternative in hormonal monitoring of infants treated for congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Secretion of 17 alpha-hydroxyprogesterone, androstenedione, and estrogens by porcine granulosa and theca interna cells in culture.

The steroid secreting activities of dispersed granulosa and theca interna cells from preovulatory follicles of prepubertal gilts 72 h after pregnant mare's serum gonadotropin treatment (750 IU) were compared. The cells were cultured for 24 h with or without steroid substrate (10(-8) to 10(-5) M progesterone, 17 alpha-hydroxyprogesterone, or androstenedione), FSH (100 ng/mL), LH (100 ng/mL), and cyanoketone (0.25 microM, an inhibitor of 3 beta-hydroxysteroid dehydrogenase). Granulosa cells cultured alone secreted mainly progesterone. Theca interna cells secreted mainly 17 alpha-hydroxyprogesterone and androstenedione, with secretion being markedly enhanced by LH. In the presence of cyanoketone, which inhibited endogenous progesterone production, theca interna but not granulosa cells were able to convert exogenous progesterone to 17 alpha-hydroxyprogesterone and androstenedione, and exogenous 17 alpha-hydroxyprogesterone to androstenedione and estradiol-17 beta in high yield. The secretion of the latter steroids from exogenous substrates was unaffected by LH. Theca interna cells secreted more estradiol-17 beta than did granulosa cells in the absence of aromatizable substrate, but estradiol-17 beta secretion by the latter was markedly increased after the addition of androstenedione. These apparent differences in steroid secreting activity between the cell types suggest that the enzymes responsible for conversion of C21 to C19 steroids, i.e., 17 alpha-hydroxylase and C17,20-lyase, reside principally in the theca interna cells. However, aromatase activity appears to be much higher in granulosa cells.

17-alpha-Hydroxyprogesterone↗
PubMed1995

[Comparison between the roles of aminoglutethimide and hydroxyprogesterone caproates in the treatment of endometrial cancer].

OBJECTIVE: To compare the changes of serum levels and tissue receptor levels of estrogen and progesterone as well as histopathological changes following treatments of endometrial cancer with aminoglutethimide (AG), progesterone caproate, or a combination of both. METHOD: Thirty-nine patients of endometrial cancer were treated with hydroxyprogesterone caproate, AG or combination of both, and their effects were compared. RESULT: It was observed that: (1) the administration of AG gave a fall of estradiol and progesterone serum levels; hydroxyprogesterone caproates therapy increased the level of progesterone; and following the combination treatment, higher progesterone and lower estradiol levels were found (P < 0.05), (2) treatments by AG as well as by combination therapy brought about a considerable fall of the positive rate of ER and PR in tissues (P < 0.05), (3) histological changes showed inhibition of cell growths in all three types of treatment, secretory cells and decidual reaction were shown under the influence of hydroxyprogesterone caproates, the changes in combination therapy mainly complied with those in AG treatment. CONCLUSION: The results suggested that AG was effective in treating patients with endometrial cancer, resulting in changes of endocrine environments and inhibition of cell growth by mechanism different from that of hydroxyprogesterone caproates.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed2005

Ketosteroid profiling using Girard T derivatives and electrospray ionization tandem mass spectrometry: direct plasma analysis of androstenedione, 17-hydroxyprogesterone and cortisol.

A function of concentrations of three ketosteroids, [(androstenedione + 17alpha-hydroxyprogesterone)/cortisol], has been shown to provide better discrimination than the concentration of 17alpha-hydroxyprogesterone alone, for the diagnosis of the inherited disease congenital adrenal hyperplasia (CAH). A rapid, direct infusion electrospray ionization tandem mass spectrometry (ESI-MS/MS) method has been developed to measure this ratio in plasma (100 microL). Sensitivity and specificity result from the preparation of mono-Girard T derivatives. Androstenedione, 17alpha-hydroxyprogesterone and cortisol are individually quantitated by isotope dilution. Excellent statistical correlation with radioimmunoassay (RIA) results for the analysis of 17alpha-hydroxyprogesterone is demonstrated. The value of the ratio function of the three ketosteroids is 0.01-0.16 for normal controls (n=26) and 1.83-18.7 for patients with severe CAH (n=4). Profiles of ketosteroids derivatized with Girard T from the plasma of a child with severe CAH, generated by ESI-MS/MS analysis, are shown. Neutral loss scans for 29.5 and 59 Da assist in the identification of the ketosteroids.

17-alpha-Hydroxyprogesterone↗
PubMed1976

In vivo and in vitro studies of 15alpha-hydroxyprogesterone in the human placenta.

Studies were conducted to determine the fate of 15alpha-hydroxyprogesterone in human placental tissue. Tritiated 15alpha-hydroxyprogesterone was perfused through normal human placentas in situ at the time of Cesarean section and incubated with a 10,000x g microsomal supernate of the placenta in vitro. In both systems the substrate, but no additional metabolites were identified. These findings indicate that 15alpha-hydroxyprogesterone is not metabolized during its passage in the human term placenta, and suggests that because of its fetal origin clinical measurements of 15alpha-hydroxyprogesterone may provide a valuable index to the status of fetal viability.

Crystallization↗
PubMed1986

Bioconversion of 16 alpha-hydroxyprogesterone to 16 alpha-hydroxylated corticosteroids by newborn rat adrenal cells in primary culture.

Using newborn rat adrenal cells in primary culture, 16 alpha-hydroxyprogesterone was bioconverted into numerous 16 alpha-hydroxylated steroids. The method of analysis of these steroids comprised the association of column and thin-layer chromatography to gas chromatography-mass spectrometry in order to obtain the mass spectra of pure compounds. The identified compounds resulted principally from the enzymatic reactions of 21-hydroxylation 11 beta-hydroxylation and reduction of the 20-oxo and 3-oxo-4-ene groups. Minor metabolites resulted from 18-hydroxylation and 6 beta-hydroxylation of the substrate. The metabolism of 16 alpha-hydroxyprogesterone is similar to that of progesterone in the same cell-culture system; however, there are two exceptions. The 21-hydroxylation of 16 alpha-hydroxyprogesterone occurs at a rate similar to that of its 11 beta-hydroxylation, whereas the 21-hydroxylation of progesterone is faster than its 11 beta-hydroxylation. The ratio of 11 beta- to 18-hydroxylation of 16 alpha-hydroxyprogesterone is about 3, whereas the ratio of 11 beta- to 18-hydroxylation of progesterone, 20 alpha-dihydroxyprogesterone and DOC is between 1./ and 2. It is most likely the rate of 18-hydroxylation which is decreased by the hydroxyl group at C-16. The use of adrenal cell cultures is a practical, simple method for the preparation of a variety of 16 alpha-hydroxylated steroids from a single substrate. Its adaptation to the production of important amounts of 16 alpha-hydroxylated corticosteroids will permit the study of their biological activity.

Adrenal Cortex Hormones↗
PubMed1981

Circadian patterns of plasma cortisol, 17-hydroxyprogesterone, and testosterone in congenital adrenal hyperplasia.

In 11 children aged between 2 and 17 years with (nonsalt-losing) congenital adrenal hyperplasia (21-hydroxylase deficiency) blood was drawn at 90-minute intervals during a 24-hour period and levels of 17-hydroxyprogesterone, testosterone, and cortisol were measured. Levels of 17-ketosteroids and pregnanetriol were measured too in 24-hour urine samples. These measurements were taken under different regimens of treatment and after interruption of treatment. Cortisol level rose and fell rapidly after administered corticosteroid, and reached unphysiologically high levels. Testosterone levels showed pronounced variations but stayed in the normal range for most of the time even in untreated patients; thus testosterone provides a poor control parameter. Levels of 17-hydroxyprogesterone showed extreme fluctuations and very high peak levels in untreated patients; standard treatment with two or three daily doses of corticosteroids did not prevent a pronounced rise in its level after midnight. After the first morning dose of hydrocortisone a very steep fall was observed. The 24-hour pregnanetriol excretion correlated well with the corresponding total integrated 17-hydroxyprogesterone area. It is concluded that single 17-hydroxyprogesterone values are unlikely to give adequate information about the quality of treatment.

17-Ketosteroids↗
PubMed1980

A simple procedure for the radioimmunoassay of 17 alpha-hydroxyprogesterone in serum: comparison with an immunological purification technique.

A simple radioimmunoassay for the measurement of 17 alpha-hydroxyprogesterone in 0.1-0.25 ml serum is described. An antibody prepared against 17 alpha-hydroxyprogesterone 3(O-carboxymethyl)-oxime-BSA as immunogen was used. A correlation of the 17 alpha-hydroxyprogesterone concentration found in the serum of normal subjects and of patients with that obtained by a more complex immunological purification method was good (r=0.924, P less than 0.001). Accuracy, precision, and specificity were acceptable with the simple method. Normal values for infants, children, and adults have been established, and the individual concentrations of 17 alpha-hydroxyprogesterone in the serum of patients withcongenital adrenal hyperplasia were well separated from normal values.

Adrenal Hyperplasia, Congenital↗
PubMed1979

Radioimmunoassay of 17 alpha-hydroxyprogesterone in saliva, parotid fluid, and plasma of congenital adrenal hyperplasia patients.

We report a radioimmunoassay sensitive enough to determine 17 alpha-hydroxyprogesterone concentrations in 200 microliter of parotid fluid or mixed whole saliva. Because the correlation of concentrations in matched samples of parotid fluid and saliva was excellent (r = 0.98), we exclusively used saliva, which is easier to collect, in later studies. The assay is specific; saliva samples assayed with and without thin-layer chromatographic purification showed no significant difference. The assay is also precise, and has a lower limit of sensitivity of 4 pg per assay tube. In 14 patients having congenital adrenal hyperplasia from a C21-hydroxylase enzyme deficiency, all of whom were receiving cortisol replacement therapy, the range in 17 alpha-hydroxyprogesterone concentrations observed in saliva (67-26,300 pmol/L) was about 20-fold that seen in 32 healthy children (90-1520 pmol/L). The close correlation (r = 0.91) between 17 alpha-hydroxyprogesterone concentrations in matched samples of saliva and plasma from these patients indicates that determination of steroids in saliva could well replace determination in plasma. This concept is supported by 17 alpha-hydroxyprogesterone concentrations monitored throughout 24 h from one patient and following stimulation with synthetic corticotropin in another patient.

Adolescent↗
PubMed1983

The effect of 17 alpha-hydroxyprogesterone caproate on pregnancy outcome in an active-duty military population.

A prior report suggested that active-duty pregnant women are at increased risk for low-birth weight infants and a higher perinatal mortality rate. The present double-blind investigation was designed to prospectively evaluate that risk and to test the efficacy of 17 alpha-hydroxyprogesterone caproate to prevent reported complications. Three groups of active-duty women were studied, beginning between 16 and 20 weeks' gestation. They were similar for parity, previous abortion, race, cigarette smoking, and marital status. Of these, 80 were given 17 alpha-hydroxyprogesterone caproate, 88 received placebo, and 78 declined to participate in the protocol. There was no significant differences in the three groups when comparisons were made for low-birth weight infants and for perinatal mortality. However, when comparison was made to a military dependent population, they had a significantly worse outcome with regard to both perinatal mortality (p = 0.001) and infants with a birth weight less than 2,500 gm (p = 0.01). We concluded that pregnant military personnel were at increased risk for adverse pregnancy outcome, but that this risk was not altered by therapy with 17 alpha-hydroxyprogesterone caproate.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1988

Comparison of separation techniques in radioimmunoassays for 17-hydroxyprogesterone.

Separation techniques have been studied in the development of a direct radioimmunoassay to determine levels of 17-hydroxyprogesterone in serum. The same highly specific sheep antiserum was used throughout, together with the same amount of 125I-labelled 17-hydroxyprogesterone to which was added sodium salicylate to eliminate interference by endogenous binding proteins in serum samples. In one approach, dextran-coated charcoal was employed to adsorb the free fraction and, in another, the antibodies were covalently coupled to magnetisable particles. The antiserum was also adsorbed to assay tubes either directly or indirectly through second (double) antibodies. Analytical recovery and specificity were similar irrespective of the separation technique as was the correlation with results obtained by a reference assay. Levels of 17-hydroxyprogesterone in sera from normal adults and from treated and untreated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency were also similar. However, the assay employing dextran-coated charcoal for separation showed the best precision and resulted in the greatest sensitivity, while the use of antibodies adsorbed indirectly to assay tubes was superior in terms of practicability.

17-alpha-Hydroxyprogesterone↗
PubMed1990

In vitro metabolism of progesterone, 17-hydroxyprogesterone, and 17,20 beta-dihydroxy-4-pregnen-3-one by ovaries of the common carp Cyprinus carpio: production rates of polar metabolites.

[14C]Progesterone, 17-[3H]hydroxyprogesterone, and 17,20 beta-[3H]dihydroxy-4-pregnen-3-one (17,20 beta P) were incubated for 1, 3, 6 or 24 hr with ovaries from carp which had received injections of either carp pituitary extract or saline. All three substrates were very rapidly metabolized to polar products, but 17,20 beta P was not detected as a metabolite of either progesterone or 17-hydroxyprogesterone. The major metabolite in all incubations was very similar, but not identical, in chemical and chromatographic properties to 5 beta-pregnane-3 alpha, 6 alpha, 17,20 beta-tetrol. A compound isopolar with 5 beta-pregnane-3 alpha, 6 alpha, 17,20 alpha-tetrol was isolated only in incubations of progesterone and 17-hydroxyprogesterone. It is suggested that hydroxylation and reduction may be a deactivation mechanism allowing 17,20 beta P to build up as an intermediate, and active maturation inducing steroid, only in response to the ovulatory gonadotrophin surge, thus assisting in synchrony of oocyte maturation.

17-alpha-Hydroxyprogesterone↗
PubMed1983

Plasma 17-hydroxyprogesterone concentrations in ill newborn infants.

Plasma 17-hydroxyprogesterone concentrations were determined in 47 preterm and term infants who were ill from a variety of causes. The results were compared with those in 53 healthy term infants. Mean plasma 17-hydroxyprogesterone values were appreciably higher in ill term and healthy preterm infants compared with healthy term infants, but the highest values were found in ill preterm infants. None of the infants had adrenal disease but some very ill infants had plasma 17-hydroxyprogesterone values approaching those seen in untreated infants with congenital adrenal hyperplasia. Interpretation of the results of plasma steroid measurements in newborn infants must take account of gestational age and the presence of stress related illness.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Diurnal variation in blood 17-hydroxyprogesterone concentrations in untreated congenital adrenal hyperplasia.

Blood spot 17-hydroxyprogesterone concentrations were measured serially over 24 hours in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency before they started treatment with glucocorticoids, and the development of diurnal rhythm in pituitary-adrenal activity was studied. Five infants aged 2 to 26 days showed an intradiem variation of 17-hydroxyprogesterone concentrations within the diagnostic range but without a characteristic diurnal pattern. Blood spot 17-hydroxyprogesterone values in a further eight patients aged 3 months to 6.5 years showed a diurnal rhythm, with high concentrations in the morning and a nadir in the evening. The results suggest that a diurnal rhythm in pituitary-adrenal activity may develop as early as the third month of life in those infants with an increased endogenous concentration of adrenocorticotrophic hormone.

17-alpha-Hydroxyprogesterone↗
PubMed1988

An automated solid-phase 17 alpha-hydroxyprogesterone ELISA method using a microtitre plate.

We report an automated ELISA method for the measurement of 17 alpha-hydroxyprogesterone in plasma samples. A rabbit antiserum raised against 17 alpha-hydroxyprogesterone-3-(O-carboxymethyl)oxime-bovine serum albumin is used for the assay and a homologous competitor 17 alpha-hydroxyprogesterone-3-(O-carboxymethyl)oxime-bovine thyroglobulin is coated onto a microtitre plate. A goat anti-rabbit IgG-horse radish peroxidase is used as a probe for this solid-phase assay. The assay exhibits good sensitivity, precision and accuracy. The method is used routinely for the management of patients with congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Progesterone and 17 alpha-hydroxyprogesterone. Novel stimulators of calcium influx in human sperm.

Progesterone and 17 alpha-hydroxyprogesterone (but not other steroids such as testosterone, corticosterone, beta-estradiol, estrone, dehydroepiandrosterone, 20 alpha-hydroxypregnen-3-one, androstenedione, and pregnenolone) were shown to cause an immediate increase, in free cytosolic calcium ([Ca2+]i) in both capacitated and noncapacitated human sperm, using the fluorescent indicator fura 2. Significant increases in [Ca2+]i were observed with 10 ng/ml progesterone, while maximum effects were seen with 1 microgram/ml progesterone. Two other steroids 11 beta-hydroxyprogesterone and 5 alpha-pregnane-3,20-dione exhibited significant activity to increase [Ca2+]i. This increase in [Ca2+]i elicited by progesterone was entirely due to Ca2+ influx from the extracellular medium since the increase in [Ca2+]i was blocked by the Ca2+ chelator EGTA (2.5 mM) and the Ca2+ channel antagonist La3+ (0.25 mM) when added to the medium containing 2.5 mM Ca2+. Progesterone also stimulated the uptake of Mn2+ into sperm as measured by the quenching of fura 2 fluorescence. Progesterone has been found in human follicular fluid at levels capable of stimulating increases in [Ca2+]i. The similarities in responses induced by human follicular fluid and progesterone an increase in [Ca2+]i, and hence the acrosome reaction, is progesterone and/or 17 alpha-hydroxyprogesterone. Progesterone (1 microgram/ml) did not increase [Ca2+]i in somatic cells such as adipocytes, hepatocytes, Balb/c 3T3 cells, normal rat kidney, or DDT1 MF-2 cells. The effects of these progestins to increase [Ca2+]i, by activating a receptor-operated calcium channel, is the first report of such an activity in sperm. This phenomena possibly opens up a new field of steroid action in the area of sterility, fertility, and contraception at the level of the sperm.

17-alpha-Hydroxyprogesterone↗